Our work on a-synuclein is currently focussed on applying large scale screening approaches to understand the pathobiology associated with this protein, which is now known to not only be a marker of disease but also plays an active role in disease progression. In ongoing work, we have been probing the mechanism by which a-synuclein is taken up from one cell to another, a process that has been proposed to be important in the spread of disease between brain regions. Using fluorescently labelled recombinant forms of a-synuclein we have initiated screens against uptake of the protein. Candidate modifiers are currently being validated to see if any are informative for mechanism of uptake, but initial results suggest that they are in a common pathway related to intracellular vesicular trafficking.